Cancer of the female genital tract and its precursors are classified into various categories according to the histopathologic changes. The prognosis of each category as a group can be assessed with a reasonable degree of accuracy. However, there is a serious limitation in the prediction of the biologic behavior in any given case solely on the basis of current histopathologic criteria. Previous studies have shown that quantitative analysis of the nuclei using nuclear DNA measurements may provide additional parameters which may correlate more accurately with the biologic potential of the lesion. In this proposal, the technique of Feulgen microspectrophotometry will be used to determine the nuclear DNA content of the following 3 major areas of gynecologic neoplasms: 1) squamous cancer of the uterine cervix and its precursors, 2) DES-related neoplastic and non-neoplastic lesions, and 3) preinvasive and invasive squamous carcinoma of the vulva. The characteristic nuclear DNA changes of the precursor conditions which are found to regress, persist and progress to more severe lesions, will be determined. Specific nuclear DNA changes that are related to the recurrence, lymph node metastasis, radiosensitivity and other treatment modalities in invasive carcinoma will be identified. Through the correlation of the nuclear DNA changes with histopathology and follow up, the ultimate objectives of this proposal are to improve our understanding of carcinogenesis in the three major areas as outlined above, to better define the morphologic criteria and to improve patient management.